In 2013, a nasal vaccine for Influenza (flu) was introduced into the routine childhood immunisation schedule, for children aged between 2 and 8 years old (NHS Gov UK, 2017). Flu strains consists of three main types (A, B and C), with A being the most dangerous and able to cause pandemics. Types B and C are progressively less severe (University of Oxford, 2017). The Fluenz Tetra vaccine is given to children, in the form of a nasal spray which protects against four types of flu: two strains of both type A and B.
Pathogenesis of Influenza
The influenza viruses are one of the most common causes of respiratory infections, and carry with them a relatively high mortality – especially in babies, people with chronic diseases and the elderly. Influenza comes from a genetically diverse group of viruses which belong to the family Orthomyxoviridae; consisting of a negative sense, single stranded RNA genome (Morens, 2008). The antigens on the different strains also vary greatly, which is why the vaccine must be redeveloped each year. For this reason, having had the disease will not protect you against all subsequent strains.
Transmission occurs primarily by aerosol or saliva from infected individuals. The virus attaches to the epithelial cells in the respiratory tract, then multiplies. This replication leads to the destruction and subsequent loss of the epithelial cells (Stegemann, 2009). Clinically, it is characterised by a rapid onset of a fever, cough, respiratory tract inflammation, headache, fatigue, muscle weakness and coryza. Most of these symptoms will last around 7-10 days, but the weakness and fatigue may persist for a few further weeks (Morens, 2008).
Influenza A viruses (IAV) with the glycoprotein hemagglutinin are able to cause pandemics, as the human immune system cannot fight these very effectively (Kawaoka & Yoshihiro, 2011). The IAV genome is a single strand of RNA consisting of eight segments, coding for hemagglutinin, neuraminidases, nucleoproteins, non-structural proteins, polymerase acidic protein and polymerase basic protein. Research has been done on the pathogenicity of influenza by reverse genetics to determine the role of each of these proteins in the course of disease. It was found that viral infection stimulates the release of type 1 interferon to produce antiviral factors – and mice without this interferon were susceptible to the virus – so it is clear that type 1 interferon plays a key role in the innate immune response to IAV (Kawaoka & Yoshihiro, 2011).
Hemagglutinin of seasonal IAV binds to glycan proteins on the epithelial cell surface in the upper respiratory tract. Inflammation from the virus is mainly restricted to this area, but nasal discharges can contain high quantities of live virus, which is how it is so easily spread throughout the population. Highly pathogenic avian influenza viruses (HPAIV) will recognise a slightly different glycan which is in the lower respiratory tract, so mostly infecting the type 2 pneumocytes in the human lung. Although these viruses are less contagious as the virus is situated much deeper in the respiratory tract, infection can result in severe pneumonia as a complication. Alongside this, one of the Polymerase basic proteins (PB1) also codes for a protein consisting of 90 amino acids, and this protein induces apoptosis in the mitochondria of infected cells (Kawaoka & Yoshihiro, 2011).
Together with virulence, host factors also play an important role in the pathogenesis of influenza viruses – with immune function of the host being the most significant. Cells recognise the viral RNA, which initiates an immune response.
When influenza viruses infect epithelial cells or alveolar macrophages, the RNA is recognised by toll-like receptor 7 (TLR7) and retinoic acid-inducible gene-I (RIG-I), both of which have signalling pathways that then lead to the production of type 1 interferon.
The virus can use protein NS1 to interfere with these signalling pathways, so that interferons are not produced – leading to a lack of innate immune response. NS1 also binds to protein kinase R (PKR), a well-known antiviral protein. This binding inhibits the antiviral properties of PKR, by reducing the regulation of viral RNA translation. This is regulated by phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α).
In addition to the type I interferon response, RIG-I and TLR7 initiate the production of inflammatory proteins – so influenza virus infection prompts the upregulation of several inflammatory cytokines and chemokines, which attract macrophages to the virus-infected lung. Macrophages with the CCR2 receptor (receptor of CCL2) express an apoptosis inducing ligand, thus leading to apoptosis of the alveolar epithelial cells.
Alongside symptoms directly from the virus, the innate immune system trying to combat viral infection can also lead to unregulated inflammation in the lungs, which can cause complications, such as exacerbation of existing respiratory conditions like asthma (Kawaoka & Yoshihiro, 2011).
Proposal for Removal from Routine Childhood Immunisation Schedule
An influenza vaccine was introduced in 2013 for children (2-8 years), to minimise the number of younger people contracting the virus and developing complications. Vaccinating younger children also helps to reduce the rate at which the virus is transmitted throughout the population. Therefore, it is less likely to reach and infect very vulnerable people (University of Oxford, 2017).
The nasal influenza vaccine is effective in preventing only 50-60% of flu cases. It must be re-administered each year due to the fact that the flu virus mutates so rapidly that the antibodies required will be constantly changing (University of Oxford, 2017). The aimed percentage of cases prevented is 60-95% (Allison & MacBain, 2011), so the nasal influenza vaccine sits below this – raising the question that it may not be effective enough to offer the degree of protection that is desired.
In Winter 2016/17, there were 1055 cases of flu – but only 60 of these were observed in schools. The majority of cases (826) arose in care homes, and 153 in hospitals (Gov UK, 2017). Since all care home residents are also entitled to a free flu vaccine (NHS choices, 2016), it cannot be said with certainty that the flu vaccine has contributed to the lower numbers of flu cases in schools.
In regions of the South (Bristol, North Somerset and South Gloucestershire), only 44% of care homes reported providing the flu vaccine to their staff, who interact with patients at very high risk of flu based complications. 38% of these care homes stated that they would not be offering the vaccine to their staff for the 2017/18 season (Public Health England, 2017). Efforts might be better focussed on vaccinating people in close contact with care home residents, and ensuring that a higher percentage of more vulnerable people receive the vaccination – rather than making it compulsory for primary school age children.
The vaccine contains attenuated flu virus and, as with everything, carries risks. It is grown in eggs, making it unsuitable for anyone who suffers from a severe egg allergy (AstraZeneca, 2017). Egg allergies are much more common in children than adults, so there will be a large percentage of children unable to receive the vaccine (University of Oxford, 2017). The nasal vaccine also contains gentamicin and gelatin, which patients may be allergic to. More than one in ten patients will experience a headache, runny nose, loss of appetite or feeling generally unwell following the vaccine (University of Oxford, 2017). Other flu-like symptoms will also affect a number of people. If the weakened vaccine reaches people who are severely immunocompromised, they may develop the disease. This does not occur with the inactivated injected vaccine given to other patients (University of Oxford, 2017). Also, the nasal vaccine cannot be administered if the patient is suffering from a runny nose (which children often do) as this increases the chance of the vaccine being ineffective (AstraZeneca, 2017).
Results currently show that the nasal flu vaccine has been working well in the UK since its introduction in 2013. However, the nasal vaccine has been used in America prior to this, and data recently showed that it was not working as effectively as it should be. As a result, the country has since ceased vaccinating children with the nasal vaccine (University of Oxford, 2017).
In conclusion, having the vaccine as part of the routine childhood vaccination schedule could be deemed unnecessary. The injected vaccine is also suitable for children who require it (NHS UK, 2016), but vaccinating otherwise healthy children (who are at low risk of flu-related complications) may have more risks to their wellbeing than benefits. As previously mentioned, efforts (financial and resources) may be better concentrated on improving the vaccine uptake in groups at higher risk of complications– which would include children with long term conditions – rather than immunising children at school age.